The elucidation of morphologic, immunologic and virologic events occurring during certain chronic conditions of the human central nervous system - viz. multiple sclerosis (MS) and subacute sclerosing panencephalitis (SSPE) are the major objectives of the proposed work. Organotypic cultures of CNS and PNS tissue and parallel in vivo experimental situations will be utilized. Lymphocytes and sera from MS patients at different stages of the disease will be tested on cultures and the effects compared with those produced in the same system by cells and sera from animals with chronic EAE and EAN. Tagging experiments will be performed to locate the sites of action of these immunologic factors in vitro. Virologic studies will involve the continued study of measles and SSPE virus infection in cultures and in CNS tissue in situ to detect specific virus-host cell relationships and differences in neurovirulence, virus assembly, and amount of virus replicated. Mutant virus effects in CNS tissue in vitro will involve the study of reovirus type III and its temperature-sensitive mutants. The mutant virus experiments may eventually extend to certain myxoviruses since a defective myxovirus (measles) has been etiologically implicated in MS. The combined study of the above in vitro and in vivo systems and the comparison of the findings with results obtained from the direct examination of CNS tissue from cases of multiple sclerosis, might yield futher information on the etiology and pathogenesis of MS.